WW domain-containing E3 ubiquitin protein ligase1 (WWP1) is reported to be upregulated in many types of human cancers; however, its expression and function in intrahepatic cholangiocarcinoma (ICC) remain unknown. Here, in this study we investigated the expression pattern, clinical prognosis, tumor biological functions, and molecular mechanisms of WWP1 in ICC. The expression of WWP1 in patient tissues was detected by western blotting, immunohistochemistry (IHC), and immunofluorescence. CCK-8, colony formation, EdU, transwell, and xenograft models were used to explore the role of WWP1 in the proliferation and metastasis of ICC. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, and immunofluorescence were performed to detect the potential mechanisms. Our study revealed that WWP1 was highly expressed in ICC, and high levels of WWP1 were associated with poor prognosis. Functionally, WWP1 overexpression enhanced the proliferation and metastasis of ICC cells and vice versa. Mechanistically, MYC could be enriched in the promoter region of WWP1 to facilitate its expression. Then, WWP1 targets Nedd4 family interacting protein1 (NDFIP1) and reduces NDFIP1 protein levels via ubiquitination. Downregulation of NDFIP1 in ICC cells rescued the effects of silenced WWP1 expression. WWP1 expression was also negatively correlated with the protein level of NDFIP1 in patient tissues. In conclusion, WWP1 upregulated by MYC promotes the progression of ICC via ubiquitination of NDFIP1, which reveals that WWP1 might be a potential therapeutic target for ICC.

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BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pancreaticoduodenectomy (PD). There is currently no widely accepted procedure for PD to reduce the incidence of DGE. Our institution attempts to perform subtotal gastrectomy in patients undergoing PD to reduce DGE. Here we aimed to evaluate the effectiveness and safety of PD with subtotal gastric resection. METHODS: Patients who underwent PD between January 2014 and December 2021 were reviewed. They were stratified by extent of gastrectomy into a conventional PD group (PD that resected approximately 1/3 of the distal stomach) and a subtotal gastrectomy PD group (PD that resected approximately 3/4 of the distal stomach), which were compared in terms of intraoperative and postoperative parameters. Result: From January 2014 to December 2021, a total of 512 patients underwent PD in the Department of Hepatobiliary Surgery, Peking University People’s Hospital. Nineteen patients were excluded from this study due to benign disease. A total of 493 patients were included, with 378 in the conventional PD group and 115 in the subtotal gastrectomy PD group. Compared with the conventional PD group, the subtotal gastrectomy PD group had a lower incidence of DGE (8.7% vs. 17.7%, p=0.019), and a shorter hospital stay. Multivariate analysis showed that conventional PD and higher body mass index were independent risk factors for grade B/C DGE. Conclusion: This study showed that, compared with conventional PD, subtotal gastrectomy PD can reduce the incidence of DGE and shorten the length of hospital stay. At the same time, subtotal gastrectomy PD is comparable to conventional PD in terms of surgical safety. Furthermore, high BMI is an independent risk factor for postoperative DGE.

Background Delayed gastric emptying (DGE) is one of the most common complications after pancreaticoduodenectomy (PD). There is currently no widely accepted procedure for PD to reduce the incidence of DGE. Our institution attempts to perform subtotal gastrectomy in patients undergoing PD to reduce DGE. Here we aimed to evaluate the effectiveness and safety of PD with subtotal gastric resection. Methods Patients who underwent PD between January 2014 and December 2021 were reviewed. They were stratified by extent of gastrectomy into a conventional PD group (PD that resected approximately 1/3 of the distal stomach) and a subtotal gastrectomy PD group (PD that resected approximately 3/4 of the distal stomach), which were compared in terms of intraoperative and postoperative parameters. Result From January 2014 to December 2021, a total of 512 patients underwent PD in the Department of Hepatobiliary Surgery, Peking University People’s Hospital. Nineteen patients were excluded from this study due to benign disease. A total of 493 patients were included, with 378 in the conventional PD group and 115 in the subtotal gastrectomy PD group. Compared with the conventional PD group, the subtotal gastrectomy PD group had a lower incidence of DGE (8.7% vs. 17.7%, p = 0.019), and a shorter hospital stay. Multivariate analysis showed that conventional PD and higher body mass index were independent risk factors for grade B/C DGE. Conclusion This study showed that, compared with conventional PD, subtotal gastrectomy PD can reduce the incidence of DGE and shorten the length of hospital stay. At the same time, subtotal gastrectomy PD is comparable to conventional PD in terms of surgical safety. Furthermore, high BMI is an independent risk factor for postoperative DGE.

e16127 Background: There are different views on the scope of indications for surgical treatment of HCC worldwide. Unlike the Barcelona Clinic Liver Cancer, the European Association for Study of the Liver, and the American Association for the Study of Liver Diseases which recommend surgical resection as the first choice only for early HCC, it is also recommended as the first treatment for selected patients with intermediate or advanced HCC in China. However, in any case, postoperative recurrence is an important issue affecting the long-term survival of HCC patients, and to date, there is no globally recognized treatment algorithm for adjuvant therapy. We performed a survey to understand the patient characteristics and clinical status of hepatobiliary surgeons’ decision aids for adjuvant treatment. Methods: This survey was conducted among senior hepatobiliary surgeons who work at high-volume hospitals in China. Surgeons were asked to fill out an online questionnaire by scanning the QR code. Results: From September to November 2021, 511 surgeons from 55 cities responded. Among them, 70.3% worked in general hospitals, 26.8% in cancer hospitals, and 2.9% in integrative medicine hospitals. The majority of the institutions were tertiary hospitals (91.2 %). When determining whether a patient was suitable or not for adjuvant therapy, surgeons mainly considered tumor factors (chosen by 92.8% and 81.6%) and patient factors (chosen by 80.8% and 75.3%). The analysis showed that the patients whom surgeons considered for adjuvant therapy had one or more of the following characteristics: Tumor factors including China liver cancer (CNLC) stage Ia-IIIb (preoperative), R1 resection, Child-Pugh A or B liver function, well recovery from surgery, presence of ≥1 high-risk recurrence factors (i.e. microvascular invasion, macrovascular tumor thrombus, and hilar lymph node metastasis); Patient factors which were hepatocarcinoma-related medical history (e.g., HBV/HCV) and affordability. Most surgeons used targeted therapy (83.8%, mainly anti-angiogenic multi-kinase inhibitors), TACE (72.8%), or combination therapy (60.3%, mainly targeted drugs combined with immunotherapy or TACE) as adjuvant therapy. When asked to choose the two most related factors impacting treatment compliance, 52.1% chose patients' financial status, and 51.7% considered adverse reactions. Less adverse reactions (71.0% of surgeons), better efficacy (66.7%), and a higher reimbursement ratio (53.3%) were the top 3 unmet need for future adjuvant therapy. Conclusions: This survey presented a patient portrait that Chinese hepatobiliary surgeons considered for adjuvant therapy and the practice patterns in adjuvant therapy for HCC. However, the patient group that can benefit from adjuvant therapy remains to be explored and validated in prospective clinical studies.